Replication Stress Induces ATR/CHK1-Dependent Nonrandom Segregation of Damaged Chromosomes.

Ataxia Telangiectasia Mutated Proteins / genetics Checkpoint Kinase 1 / genetics Chromosome Segregation Chromosomes, Human / genetics DNA Damage DNA Replication HeLa Cells Humans Mitosis Signal Transduction
ATR/CHK1 asymmetric DNA damage response biased inheritance nonrandom DNA segregation replication stress

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
21 05 2020
Historique:
received: 30 10 2019
revised: 22 02 2020
accepted: 06 04 2020
pubmed: 1 5 2020
medline: 25 8 2020
entrez: 1 5 2020
Statut: ppublish

Résumé

Nonrandom DNA segregation (NDS) is a mitotic event in which sister chromatids carrying the oldest DNA strands are inherited exclusively by one of the two daughter cells. Although this phenomenon has been observed across various organisms, the mechanism and physiological relevance of this event remain poorly defined. Here, we demonstrate that DNA replication stress can trigger NDS in human cells. This biased inheritance of old template DNA is associated with the asymmetric DNA damage response (DDR), which derives at least in part from telomeric DNA. Mechanistically, we reveal that the ATR/CHK1 signaling pathway plays an essential role in mediating NDS. We show that this biased segregation process leads to cell-cycle arrest and cell death in damaged daughter cells inheriting newly replicated DNA. These data therefore identify a key role for NDS in the maintenance of genomic integrity within cancer cell populations undergoing replication stress due to oncogene activation.

Identifiants

DOI: 10.1016/j.molcel.2020.04.005 PMID: 32353258
pubmed: 32353258
pii: S1097-2765(20)30231-8
doi: 10.1016/j.molcel.2020.04.005
pii:
doi:

Substances chimiques

ATM protein, human EC 2.7.11.1
ATR protein, human EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins EC 2.7.11.1
CHEK1 protein, human EC 2.7.11.1
Checkpoint Kinase 1 EC 2.7.11.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

714-724.e5

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Meichun Xing (M)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Fengjiao Zhang (F)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Hongwei Liao (H)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Sisi Chen (S)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Luanqing Che (L)

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Xiaohui Wang (X)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Zhengqiang Bao (Z)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Fang Ji (F)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Gaoying Chen (G)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Huihui Zhang (H)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.

Wen Li (W)

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Zhihua Chen (Z)

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.

Ying Liu (Y)

Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.

Ian D Hickson (ID)

Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark. Electronic address: iandh@sund.ku.dk.

Huahao Shen (H)

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong 510120, China. Electronic address: huahaoshen@zju.edu.cn.

Songmin Ying (S)

Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China. Electronic address: yings@zju.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines nucléaires › Protéines liant le poly-adp-ribose › Protéines mutées dans l'ataxie-télangiectasie › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Checkpoint kinase 1 › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Phénomènes génétiques › Division du noyau cellulaire › Ségrégation des chromosomes › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Phénomènes génétiques › Altération de l'ADN › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Phénomènes génétiques › Réplication de l'ADN › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HeLa › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Phénomènes génétiques › Division du noyau cellulaire › Mitose › Replication Stress Induces ATR/CHK1-Dependent...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Replication Stress Induces ATR/CHK1-Dependent...